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51.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
52.
OBJECTIVE: Androgenic progestins such as norethisterone acetate (NETA) may influence the effect of estradiol (E(2)) therapy. We compared the influence of oral E(2), with and without NETA, and transdermal E(2) on markers of coagulation, fibrinolysis, and inflammation and on lipids and lipoproteins in healthy postmenopausal women. DESIGN: A total of 112 healthy postmenopausal women were randomized to receive treatment with either oral E(2), with or without NETA, transdermal E(2), or placebo. At baseline and after 28 weeks, levels of serum lipids and lipoproteins and markers of coagulation, fibrinolysis, and inflammation were determined. RESULTS: Of the fibrinolytic parameters, oral E(2) (P < 0.05) and E(2) with NETA (P < 0.01) shortened euglobulin clot lysis time. Oral E(2) decreased plasminogen activator inhibitor-1 activity (P < 0.05). Oral E(2) with NETA reduced plasminogen activator inhibitor-1 antigen levels (P < 0.01) and increased D-dimer antigen levels (P < 0.001). All three modes of menopausal hormone therapy reduced tissue type plasminogen activator antigen. Of the coagulation parameters, both routes of E(2) therapy decreased fibrinogen levels (P = 0.002 for oral and P = 0.007 for transdermal E(2)), whereas E(2) with NETA showed no effect. The decrease of fibrinogen was larger after oral E(2) (P = 0.02). Oral E(2) with NETA reduced antithrombin III (P < 0.001) and protein C (P < 0.001) activity. Oral E(2) (P = 0.04) and E(2) with NETA (P < 0.01) increased C-reactive protein (CRP). Transdermal E(2) showed no influence on CRP. The addition of NETA influenced the change in CRP, as the increase in CRP was more pronounced after E(2) without NETA (P = 0.005). The levels of serum amyloid A, interleukin-6, and tumor necrosis factor-alpha did not change significantly after any of the modes of hormone therapy. Of the lipids and lipoproteins, oral E2 decreased low-density lipoprotein cholesterol (P < 0.01), lipoprotein (a) (P < 0.05), and increased high-density lipoprotein cholesterol (P < 0.05). Transdermal E(2) decreased triglycerides (P < 0.02) and increased high-density lipoprotein cholesterol (P < 0.03). Oral E(2) with NETA decreased total cholesterol (P < 0.01) and high-density lipoprotein cholesterol (P < 0.005). CONCLUSIONS: Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis. Both modes of oral menopausal hormone therapy have a greater impact on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins than transdermal E(2). NETA attenuates some E(2) effects. Further studies are needed to elucidate the impact of these effects on clinical endpoints. 相似文献
53.
Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes. 相似文献
54.
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56.
KAP Meeuwis JA De Hullu MEA De Jager LFAG Massuger PCM Van De Kerkhof MM Van Rossum 《Journal of the European Academy of Dermatology and Venereology》2010,24(12):1425-1430
Background Psoriatic lesions may involve nearly all sites of the body. Involvement of the genital skin is frequently classified as part of intertriginous psoriasis without special awareness and treatment for this presentation of the disease. Gaining knowledge about the frequency of the involvement of genital skin in these patients will improve the overall care for patients with psoriasis. Objectives We studied the prevalence of genital psoriasis in the Netherlands and epidemiological characteristics of this specific presentation of the disease. Furthermore, we studied the relation between flexural and genital psoriasis. Patients/Methods A self‐administered questionnaire was sent to all 5300 members of the Dutch Psoriasis Society. Sociodemographic patient characteristics and disease‐related data (such as localization of psoriatic lesions, involvement of the genitalia, age at onset of genital psoriasis and severity of genital psoriatic lesions) were collected and analysed. Results A response rate of 37% was achieved. Almost 46% of the responding patients with psoriasis, that is 16.5% of all potential responders (n = 5300), report genital involvement at some time during the course of their disease. The genitalia can become affected at any age. Many patients with current genital involvement (38%) do not have the flexural skin affected. Conclusions A large part of patients with psoriasis suffer from genital psoriasis, which was not associated with flexural involvement in at least one third of them. More attention to the genital region is required in the current standard treatment of both male and female psoriatic patients at any age. 相似文献
57.
MM Gorham-Rowan 《The European journal of contraception & reproductive health care》2013,18(3):166-172
Objectives To compare objective voice measures of vocal stability during different speech tasks in women taking oral contraceptives to those in women not taking oral contraceptives. Methods Voice recordings obtained from 28 women, aged 20-30 years old, were used for the study. Eighteen of the women were taking some form of oral contraception at the time of the recording (OC women); ten women were not taking any oral contraceptive medication (NOC women). Measures related to pitch, vocal stability, and loudness were obtained from sustained vowel and paragraph reading tasks. Results The OC women demonstrated significantly higher pitch levels but lower values related to measures of vocal stability. Conclusions The use of oral contraceptives appears to exert a positive influence upon vocal fold function. Women taking oral contraceptives demonstrate higher pitch levels and greater stability during phonation than do women not taking oral contraceptives. This improvement in vocal function is contributed to the more stable hormonal environment that occurs with the use of oral contraceptives. 相似文献
58.
Osteomyelitis: detection with US 总被引:2,自引:0,他引:2
To evaluate the role of ultrasound (US) in the detection of osteomyelitis, the authors prospectively studied 48 patients clinically suspected of having osteomyelitis. A sonographic diagnosis was made if fluid was seen directly in contact with bone, without intervening soft tissues. Twelve of the 48 patients were subsequently found to have osteomyelitis. In 10 of them, US demonstrated abnormal fluid adjacent to the bone. This fluid was thought to represent an inflammatory exudate dissecting in a subperiosteal and/or extraperiosteal location. Eight of the 48 patients had soft-tissue fluid collections. The rest of the patients either had no abnormalities or had cellulitis. The authors conclude that US can be useful in the detection of osteomyelitis. 相似文献
59.
研究发现银屑病皮损能够高度聚集原卟啉Ⅸ(PpⅨ,一种由5-ALA产生的内源性光源物质),但进行荧光诊断时却发现皮损内PpⅨ的分布存在差异,造成这种差异的原因目前尚不清楚。 相似文献
60.
De‐hui Zhang MM Zheng‐qing Wu MB Xin‐cheng Zuo MD Jian‐wei Li MM Chang‐lin Huang MB 《Orthopaedic Surgery》2011,3(1):35-39
Objective: To investigate the diagnosis and surgical treatment of excessive lateral pressure syndrome of the patellofemoral joint caused by military training. Methods: Fifteen patients (patient group) and 18 healthy volunteers (control group) were involved in this retrospective study. Radiographs of the knee joints of all patients and volunteers were taken. The bone architecture was assessed, the trochlear angle, coincidence angle and patellofemoral joint index measured in both groups, and the resulting data compared. All 15 patients (17 knees) were treated by lateral collateral retinaculum release. Pre‐ and post‐operative pain was evaluated with a visual analog scale (VAS). Results: The differences between the two groups in coincidence angle (patient group: 7.67°± 5.81°; control group: ?2.2°±?2.71°) and patellofemoral joint index (patient group: 2.49 ± 1.40; control group: 1.25 ± 0.15) were statistically significant. Subchondral bone sclerosis and osteophytosis in the patellofemoral joint were more pronounced in the patient group than in the control group. The VAS was higher preoperatively (7.06 ± 0.85) than postoperatively (6 months postoperatively: 3.87 ± 0.24; 1 year postoperatively: 3.01 ± 0.17), and the differences between preoperative and postoperative were statistically significant. Conclusions: Apart from the case history, typical symptoms and physical signs, X‐ray examination is the most basic way to diagnose excessive lateral pressure syndrome of the patellofemoral joint, and the patellofemoral joint index is the most reliable for diagnosis. Lateral collateral retinaculum release with a small‐incision is an effective treatment for this disease. 相似文献